Site-directed mutagenesis of esterases

ABSTRACT

A method of modifying esterases by substitution with histadine of at least one amino acid within 6 Å of an active site serine provides esterases useful for detoxifying organophasphates.

FIELD OF THE INVENTION

This invention relates to use of organophosphorus acid anhydride (OPAA) hydrolyzing enzymes to detoxify organophosphates (OP) using site directed mutagenesis of esterases that strongly bind OP compounds, including acetylcholinesterases, butyrylcholinesterases, carboxylesterases and lipases.

BACKGROUND OF THE INVENTION

Poisoning with organophosphates presents a problem for agricultural workers that must be exposed to some agricultural chemicals and to military personnel exposed to chemicals used in chemical warfare. Furthermore the stock-piling of organophosphates has resulted in need to find ways to detoxify such stocks, including decontamination of land where OP's have been stored.

Present treatment for poisoning by organophosphates (OP) consists of a combination of drugs such as carbamates (e.g., pyridostigmine), anti-muscarinic (e.g., atropine), and reactivators (e.g., 2-[hydroxyiminomethyl]-1-methylpyridinium chloride, pralidoxime chloride) administered in post-exposure modalities. Although this drug regimen is effective in protecting experimental animals against lethality by OP poisoning, it is not effective in preventing convulsions, performance deficits, or permanent brain damage. To alleviate these post-exposure symptoms, the use of cholinesterases (ChEs) as a pretreatment drug was successfully tested in animals including non-human primates for the sequestration of highly toxic OP anti-ChEs before they reach their physiological targets. For example, pretreatment of rhesus monkeys with FBS AChE or horse serum butyrylcholinesterase protected them against a challenge up to 5 LD₅₀ of O-pinacolyl methylphosphonofluoridate (soman), a highly toxic OP. These monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task or the primate equilibrium platform performance task. In vivo and in vitro titration of ChEs with a variety of OPs produce a 1:1 stoichiometry between organophosphate inhibited enzymes and the cumulative dose of the toxic nerve agent. These results substantiated the hypothesis that exogenously administered ChEs can effectively sequester in vivo OPs before they reach their physiological targets.

Although the use of cholinesterases as a single pretreatment drug for highly potent OPs is sufficient to provide complete protection without the need for postexposure treatment, its practical use at the present time may be limited. Large quantities of enzymes will be required to provide sufficient protection due to 1:1 stoichiometry (i.e., a single turnover) between OP and enzyme required to provide protection.

Various approaches have been considered for improving the efficacy of ChEs as pretreatment drugs. First, production of catalytic antibodies that hydrolyze OPs has been attempted. The second approach is the use of hydrolytic enzymes such as OP hydrolases. Parathion hydrolase from bacteria was shown to hydrolyze tabun with a sufficient rate to be useful as a pretreatment drug but it has a very short half-life in mice, but did provide protection from soman at dosage of 2 LD₅₀.

SUMMARY OF THE INVENTION

It is a purpose of this invention to provide improved means for detoxifying organophosphates by use of mutant esterases. In a preferred embodiment a butyrylcholinesterase which is particularly effective in detoxifying sites contaminated with OP's is exemplified. A human butyrylcholinesterase in which the glycine residue at the 117 position is substituted by histidine (identified as G117H) was particularly resistent to inactivation by OPAA and particularly effective for use in detoxification of organophosphorus anti-cholinesterase compounds. The method of detoxifying an organophosphate consists of (1) modifying an esterase by substitution with histadine of at least one amino acid within 6 angstrom units (A) of an active site serine and (2) contacting the organophosphate with a composition containing at least one of the esterases produced by step (1).

DETAILED DESCRIPTION OF THE INVENTION

It is the purpose of this invention to produce organophosporus acid anhydride (OPAA) hydrolyzing enzyme by site-directed mutagenesis of esterases that are stongly inhibited by OPAA compounds, including acetylcholinesterases, butyrylcholinesterases, and lipases. One example of such an esterase is the butyrylchoninesterase mutant identified as G117H wherein a glycine residue at position 117 is substituted by histidine. This mutant has been shown to be particularly effective for catalyzing the hydrolysis of sarin (isopropyl methylphosphonofluoridate, DFP (diisopropyl phosphorofluoridate), VX (o-ethyl-S-[2-bis(methylethyl)aminoethyl] methylphosphonothioate and Echothiophate. Furthermore, G117H was shown to be highly resistant to inhibition by organophosphorus inhibitors while maintaining its ability to catalyze the hydrolysis of normal substrates such as acetylcholine, butyrylcholine, acetylthiocholine, butyrylthiocholine, 4-nitophenyacetate and benzoylcholine.

The mutant enzymes present several advantages over the naturally-occurring OPAA hydrolyzing enzymes, showing increased efficiency. For example, G117H is able to catalyze the hydrolysis of VX at 25° C., pH 7.5 with turnover number of 5×10⁻⁴ per second, which represents more than 350 fold increase over spontaneous hydrolysis under the same conditions. None of the naturally occurring OPAA hydrolases catalyze the hydrolysis of VX.

The mutants were prepared by site-directed mutagenesis using a conventional oligonucleotide directed in vitro mutagenesis system described by Eckstein and co-workers in Nucleic Acids Research 13, 8749-8785 (1985). Other conventional PCR techniques known in the art may be used. The selection of residues for replacement was based on a molecular model, using the crystal structure of AcChE published by Sussman, et al. on an Evans and Sutherland PS390 platform with Biosym software. This is really the critical factor; once the appropriate residue has been identified the mutagenesis is quite straightforward.

The nature of the residue being displaced is irrelevant so long as it is not critical for the maintenance of the structure of the protein. The important factor is the position of the substituted residue with respect to the active site serine. Usually the preferred substitution involves replacement of at least one amino acid with a histidine. We know that substitution at most other sites would have no effect at all, unless it disrupted the structure of the protein.

The cholinesterases of the invention can be produced in accord with the teachings of Fischer, U.S. Pat. No. 5,248,604, which is incorporated herein by reference in its entirety.

The butyryl cholinesterase and acetylcholinesterase have been modified extensively in the manner described.

    Human Butyrylcholinesterase - Wild Type (unmutated)                                                                             - MHSKVTIICIRFLFWFLLLCMLI                                                    GKSHTEDDIIIATKNGKVRGMNLTVFG                                                    GTVTAFLGIPYAQ (Seq. #1)                                                          - PPLGRLRFKKPQSLTKWSDIWNA                                                    TKYANSCCQNIDQSFPGFHGSEMWNPN                                                    TDLSEDCLYLNVW                      - IPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALGFLALPGNPE                                                            - APGNMGLFDQQLALQWVQKNIAA                                                    FGGNPKSVTLFGESAGAASVSLHLLSP                                                    GSHSLFTRAILQS                      - GSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLS                                                            - VNFGPTVDGDFLTDMPDILLELG                                                    QFKKTQILVGVNKDEGTAFLVYGAPGF                                                    SKDNNSIITRKEF                      - QEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFICPALEFTKKFSEWG                                                            - NNAFFYYFEHRSSKLPWPEWMGV                                                    MHGYEIEFVFGLPLERRDNYTKAEEIL                                                    SRSIVKRWANFAK                      - YGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMTKLRAQQCRFWTSFFPKVLEMTGNIDEA                                                            - EWEWKAGFHRWNNYMMDWKNQFN                                                    DYTSKKESCVGL                       - Human BuChE G117-->H                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ (Seq                                                     #2)                                - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGHFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE L286-->H                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #3)                          - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPHS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      -  - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                       - Human BuChE L286-->H                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #4)                          - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPHS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPP                                                        (Seq. #5)                          - LGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAP                                                          - KPKNATVLIWIYGGGFQTGTSSL                                                    HVYDGKFLARVERVIVVSMNYRVGALG                                                    FLALPGNPEAPGNMG                    - LFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQSGSFNAPWA                                                          - VTSLYEARNRTLNLAKLTGCSRE                                                    NETEIIKCLRNKDPQEILLNEAFVVPY                                                    GTPLSHNFGPTVDGD                    - FLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEFQEGLKIFFPGVS                                                          - EFGKESILFHYTDWVDDQRPENY                                                    REALGDVVGDYNFICPALEFTKKFSEW                                                    GNNAFFYYFEHRSSK                    - LPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPV                                                          - FKSTEQKYLTLNTESTRIMTKLR                                                    AQQCRFWTSFFPKVLEMTGNIDEAEWE                                                    WKAGFHRWNNYMMDW                    - KNQFNDYTSKKESCVGL                                                            - Human BuChE G117-->K                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #6)                          - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGKFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE G117-->C                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #7)                          - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGCFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE G117-->H, Q119-->E                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #8)                          - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGHFETG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE L286-->H, F329-->D                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #9)                          - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPHS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTADLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE L286-->H, F329-->E                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #10)                         - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPHS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAELVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H, G291-->E                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #11)                         - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - HNFEPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H, G291-->D                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #12)                         - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - HNFDPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE H119-->H                                                         - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ (Seq                                                     #13)                               - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFHTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - VNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE Q119-->H, V288-->E                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ (Seq                                                     #14)                               - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFHTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - ENFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H, Q119-->D                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ (Seq                                                     #15)                               - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFDTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - HNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H, Q119-->E                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ (Seq                                                     #16)                               - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFDTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEAFVVPYGTPLS                      - HNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H, A277-->D                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #17)                         - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEDFVVPYGTPLS                      - HNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          - Human BuChE V288-->H, A277-->E                                               - MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQ                                                          (Seq. #18)                         - PPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVW                                                            - IPAPKPKNATVLIWIYGGGFQTG                                                    TSSLHVYDGKFLARVERVIVVSMNYRV                                                    GALGFLALPGNPE                      - APGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQS                                                            - GSFNAPWAVTSLYEARNRTLNLA                                                    KLTGCSRENETEIIKCLRNKDPQEILL                                                    NEEFVVPYGTPLS                      - HNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEF                                                            - QEGLKIFFPGVSEFGKESILFHY                                                    TDWVDDQRPENYREALGDVVGDYNFIC                                                    PALEFTKKFSEWG                      - NNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAK                                                            - YGNPNETQNNSTSWPVFKSTEQK                                                    YLTLNTESTRIMTKLRAQQCRFWTSFF                                                    PKVLEMTGNIDEA                      - EWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL                                          -      The acetylcholinesterase was also mutated in similiar                  fashion.                                                                        - Human Acetylcholinesterase (AChE; EC 3.1.1.7) Wildtype                       - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF                                                          (Seq. #19)                         - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGGFYSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              - Human AChE G121-->H                                                          - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF                                                          (Seq. #20)                         - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGHFYSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              - Human AChE F290-->H                                                          - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF                                                          (Seq. #21)                         - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGGFYSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVHRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              - Human AChE F290-->H, F333-->D                                                - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF (Seq                                                     #22)                               - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGGFYSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVHRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYDLVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              - Human AChE F290-->H, F333-->E                                                - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF (Seq                                                     #23)                               - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGGFYSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVHRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYELVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              - Human AChE Y123-->H                                                          - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF                                                          (Seq. #24)                         - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGGFYSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVFRHSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              - Human AChE Y123-->H                                                          - MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAF                                                          (Seq. #25)                         - LGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSED                                                            - CLYLNVWTPYPRPTSPTPVLVWI                                                    YGGGFHSGASSLDVYDGRFLVQAERTV                                                    LVSMNYRVGAFGF                      - LALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGL                                                            - FHRAVLQSGAPNGPWATVGMGEA                                                    RRRATQLAHLVGCPPGGTGGNDTELVA                                                    CLRTRPAQVLVNH                      - EWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFS                                                            - KDNESLISRAEFLAGVRVGVPQV                                                    SDLAAEAVVLHYTDWLHPEDPARLREA                                                    LSDVVGDHNVVCP                      - VAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFA                                                            - QRLMRYWANFARTGDPNEPRDPK                                                    APQWPPYTAGAQQYVSLDLRPLEVRRG                                                    LRAQACAFWNRFL                      - PKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL                              -      Carboxylesterase was also mutated.                                      - Human Liver Carboxylesterase (CaE) Wildtype                                  - EHCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWG (Seq                                                     #26)                               - FFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNL                                                            - FHRAISESGVALTSVLVKKGDVK                                                    PLAEQIAITAGCKTTTSAAMVHCLRQK                                                    TEEELLETTLKIG                      - NSYLWTYRETQRESTLLGTVIDGMLLLKTPEELQRERNFHTVPYMVGINKQEFGWLIPMQLMS                                                            - YPLSEGQLDQKTAMSLLGSPIPL                                                    FAIAKELIPEATEKYLGGTDDTVKKKD                                                    LILDLIADVMFGV                      - PSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIR                                                            - LSKMVMKFWANFARNGNPNGKGL                                                    PHWPEYNQKEGYLQIGANTQAAQKLKD                                                    KEVAFWTNLFAKK                      - AVEKPPQTDHIEL                                                                - Human Liver Carboxylesterase (CaE) G30-->H                                   - EHCLYLNIYTPADLTKKNRLPVMVWIHGGHLMVGAASTYDGLALAAHENVVVVTIQYRLGIWG (Seq                                                     #27)                               - FFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNL                                                            - FHRAISESGVALTSVLVKKGDVK                                                    PLAEQIAITAGCKTTTSAAMVHCLRQK                                                    TEEELLETTLKIG                      - NSYLWTYRETQRESTLLGTVIDGMLLLKTPEELQRERNFHTVPYMVGINKQEFGWLIPMQLMS                                                            - YPLSEGQLDQKTAMSLLGSPIPL                                                    FAIAKELIPEATEKYLGGTDDTVKKKD                                                    LILDLIADVMFGV                      - PSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIR                                                            - LSKMVMKFWANFARNGNPNGKGL                                                    PHWPEYNQKEGYLQIGANTQAAQKLKD                                                    KEVAFWTNLFAKK                      - AVEKPPQTDHIEL                                                                - Human CaE G30-->H, M32-->E                                                   - EHCLYLNIYTPADLTKKNRLPVMVWIHGGHLEVGAASTYDGLALAAHENVVVVTIQYRLGIWG (Seq                                                     #28)                               - FFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNL                                                            - FHRAISESGVALTSVLVKKGDVK                                                    PLAEQIAITAGCKTTTSAAMVHCLRQK                                                    TEEELLETTLKIG                      - NSYLWTYRETQRESTLLGTVIDGMLLLKTPEELQRERNFHTVPYMVGINKQEFGWLIPMQLMS                                                            - YPLSEGQLDQKTAMSLLGSPIPL                                                    FAIAKELIPEATEKYLGGTDDTVKKKD                                                    LILDLIADVMFGV                      - PSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIR                                                            - LSKMVMKFWANFARNGNPNGKGL                                                    PHWPEYNQKEGYLQIGANTQAAQKLKD                                                    KEVAFWTNLFAKK                      - AVEKPPQTDHIEL                                                                - Human CaE G30-->H, M32-->D                                                   - EHCLYLNIYTPADLTKKNRLPVMVWIHGGHLDVGAASTYDGLALAAHENVVVVTIQYRLGIWG                                                          (Seq. #29)                         - FFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNL                                                            - FHRAISESGVALTSVLVKKGDVK                                                    PLAEQIAITAGCKTTTSAAMVHCLRQK                                                    TEEELLETTLKIG                      - NSYLWTYRETQRESTLLGTVIDGMLLLKTPEELQRERNFHTVPYMVGINKQEFGWLIPMQLMS                                                            - YPLSEGQLDQKTAMSLLGSPIPL                                                    FAIAKELIPEATEKYLGGTDDTVKKKD                                                    LILDLIADVMFGV                      - PSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIR                                                            - LSKMVMKFWANFARNGNPNGKGL                                                    PHWPEYNQKEGYLQIGANTQAAQKLKD                                                    KEVAFWTNLFAKK                      - AVEKPPQTDHIEL                                                                - Human CaE E202-->H                                                           - EHCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWG                                                          (Seq. #30)                         - FFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNL                                                            - FHRAISESGVALTSVLVKKGDVK                                                    PLAEQIAITAGCKTTTSAAMVHCLRQK                                                    TEEELLETTLKIG                      - NSYLWTYRETQRHSTLLGTVIDGMLLLKTPEELQRERNFHTVPYMVGINKQEFGWLIPMQLMS                                                            - YPLSEGQLDQKTAMSLLGSPIPL                                                    FAIAKELIPEATEKYLGGTDDTVKKKD                                                    LILDLIADVMFGV                      - PSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIR                                                            - LSKMVMKFWANFARNGNPNGKGL                                                    PHWPEYNQKEGYLQIGANTQAAQKLKD                                                    KEVAFWTNLFAKK                      - AVEKPPQTDHIEL                                                                - Human CaE T204-->H                                                           - EHCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWG (Seq                                                     #31)                               - FFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNL                                                            - FHRAISESGVALTSVLVKKGDVK                                                    PLAEQIAITAGCKTTTSAAMVHCLRQK                                                    TEEELLETTLKIG                      - NSYLWTYRETQRESHLLGTVIDGMLLLKTPEELQRERNFHTVPYMVGINKQEFGWLIPMQLMS                                                            - YPLSEGQLDQKTAMSLLGSPIPL                                                    FAIAKELIPEATEKYLGGTDDTVKKKD                                                    LILDLIADVMFGV                      - PSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIR                                                            - LSKMVMKFWANFARNGNPNGKGL                                                    PHWPEYNQKEGYLQIGANTQAAQKLKD                                                    KEVAFWTNLFAKK                      - AVEKPPQTDHIEL                                                        

If the catalyst is to be used in vitro to destroy nerve agent stocks it could simply be stirred into an aqueous solution of the nerve agent and allowed to stand at ambient temperature for a time. For in vivo use as a pretreatment against nerve agent exposure it could be administered parenterally (for example, intravenously, subcutaneously or intramuscularly, or delivered via inhalation via a gene transfer vector. There is no need for an oxime with these mutants.

Kinetic data, both substrate hydrolysis and reaction with inhibitors for mutant BuChE G117H that compares the mutant with the wild type enzyme, is provided. Specifically, K_(m) and V_(max) for hydrolysis of benzoylcholine, acetylthiocholine, butyrylthiocholine and p-nitrophenyl acetate have been compared. Data also shows comparison of inhibition and reactivation rates for GA, GB, GD, VX, DFP, and Echothiophate using the G117H.

As indicated previously, the nature of the residue being displaced is irrelevant so long as it is not critical for the maintenance of the structure of the protein. The important factor is the position of the substituted residue with respect to the active site serine in the folded molecule.

    __________________________________________________________________________     #             SEQUENCE LISTING                                                    - -  - - (1) GENERAL INFORMATION:                                              - -    (iii) NUMBER OF SEQUENCES: 31                                           - -  - - (2) INFORMATION FOR SEQ ID NO:1:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                                - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp         Phe                                                                              1               5   - #                10  - #                15               - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:2:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - His Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:3:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro His Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:4:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro His Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:5:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:6:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Lys Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:7:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Cys Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:8:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - His Phe Glu Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:9:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:                           - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro His Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Asp Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:10:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro His Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Glu Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:11:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Glu Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:12:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Asp Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:13:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe His Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:14:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe His Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Glu Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:15:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Asp Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:16:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Asp Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:17:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Asp Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:18:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:                          - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Glu Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r His Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - (2) INFORMATION FOR SEQ ID NO:19:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 614 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:                          - - Met Arg Pro Pro Gln Cys Leu Leu His Thr Pr - #o Ser Leu Ala Ser Pro       1               5   - #                10  - #                15                - - Leu Leu Leu Leu Leu Leu Trp Leu Leu Gly Gl - #y Gly Val Gly Ala Glu                   20      - #            25      - #            30                    - - Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Va - #l Arg Gly Gly Arg Leu               35          - #        40          - #        45                        - - Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pr - #o Val Ser Ala Phe Leu           50              - #    55              - #    60                            - - Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pr - #o Arg Arg Phe Leu Pro       65                  - #70                  - #75                  - #80         - - Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Va - #l Asp Ala Thr Thr Phe                       85  - #                90  - #                95                - - Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Le - #u Tyr Pro Gly Phe Glu                   100      - #           105      - #           110                   - - Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Le - #u Ser Glu Asp Cys Leu               115          - #       120          - #       125                       - - Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pr - #o Thr Ser Pro Thr Pro           130              - #   135              - #   140                           - - Val Leu Val Trp Ile Tyr Gly Gly Gly Phe Ty - #r Ser Gly Ala Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gl - #n Ala Glu Arg Thr         Val                                                                                              165  - #               170  - #               175              - - Leu Val Ser Met Asn Tyr Arg Val Gly Ala Ph - #e Gly Phe Leu Ala Leu                   180      - #           185      - #           190                   - - Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gl - #y Leu Leu Asp Gln Arg               195          - #       200          - #       205                       - - Leu Ala Leu Gln Trp Val Gln Glu Asn Val Al - #a Ala Phe Gly Gly Asp           210              - #   215              - #   220                           - - Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Al - #a Gly Ala Ala Ser Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Met His Leu Leu Ser Pro Pro Ser Arg Gl - #y Leu Phe His Arg         Ala                                                                                              245  - #               250  - #               255              - - Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Tr - #p Ala Thr Val Gly Met                   260      - #           265      - #           270                   - - Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Al - #a His Leu Val Gly Cys               275          - #       280          - #       285                       - - Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Gl - #u Leu Val Ala Cys Leu           290              - #   295              - #   300                           - - Arg Thr Arg Pro Ala Gln Val Leu Val Asn Hi - #s Glu Trp His Val Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Va - #l Pro Val Val Asp         Gly                                                                                              325  - #               330  - #               335              - - Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Il - #e Asn Ala Gly Asp Phe                   340      - #           345      - #           350                   - - His Gly Leu Gln Val Leu Val Gly Val Val Ly - #s Asp Glu Gly Ser Tyr               355          - #       360          - #       365                       - - Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Ly - #s Asp Asn Glu Ser Leu           370              - #   375              - #   380                           - - Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Ar - #g Val Gly Val Pro Gln       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Ser Asp Leu Ala Ala Glu Ala Val Val Le - #u His Tyr Thr Asp         Trp                                                                                              405  - #               410  - #               415              - - Leu His Pro Glu Asp Pro Ala Arg Leu Arg Gl - #u Ala Leu Ser Asp Val                   420      - #           425      - #           430                   - - Val Gly Asp His Asn Val Val Cys Pro Val Al - #a Gln Leu Ala Gly Arg               435          - #       440          - #       445                       - - Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Ty - #r Val Phe Glu His Arg           450              - #   455              - #   460                           - - Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gl - #y Val Pro His Gly Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu As - #p Pro Ser Arg Asn         Tyr                                                                                              485  - #               490  - #               495              - - Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Le - #u Met Arg Tyr Trp Ala                   500      - #           505      - #           510                   - - Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pr - #o Arg Asp Pro Lys Ala               515          - #       520          - #       525                       - - Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gl - #n Gln Tyr Val Ser Leu           530              - #   535              - #   540                           - - Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Le - #u Arg Ala Gln Ala Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Le - #u Ser Ala Thr Asp         Thr                                                                                              565  - #               570  - #               575              - - Leu Asp Glu Ala Glu Arg Gln Trp Lys Ala Gl - #u Phe His Arg Trp Ser                   580      - #           585      - #           590                   - - Ser Tyr Met Val His Trp Lys Asn Gln Phe As - #p His Tyr Ser Lys Gln               595          - #       600          - #       605                       - -      Asp Arg Cys Ser Asp Leu                                                       610                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:20:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 614 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:                          - - Met Arg Pro Pro Gln Cys Leu Leu His Thr Pr - #o Ser Leu Ala Ser Pro       1               5   - #                10  - #                15                - - Leu Leu Leu Leu Leu Leu Trp Leu Leu Gly Gl - #y Gly Val Gly Ala Glu                   20      - #            25      - #            30                    - - Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Va - #l Arg Gly Gly Arg Leu               35          - #        40          - #        45                        - - Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pr - #o Val Ser Ala Phe Leu           50              - #    55              - #    60                            - - Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pr - #o Arg Arg Phe Leu Pro       65                  - #70                  - #75                  - #80         - - Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Va - #l Asp Ala Thr Thr Phe                       85  - #                90  - #                95                - - Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Le - #u Tyr Pro Gly Phe Glu                   100      - #           105      - #           110                   - - Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Le - #u Ser Glu Asp Cys Leu               115          - #       120          - #       125                       - - Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pr - #o Thr Ser Pro Thr Pro           130              - #   135              - #   140                           - - Val Leu Val Trp Ile Tyr Gly Gly His Phe Ty - #r Ser Gly Ala Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gl - #n Ala Glu Arg Thr         Val                                                                                              165  - #               170  - #               175              - - Leu Val Ser Met Asn Tyr Arg Val Gly Ala Ph - #e Gly Phe Leu Ala Leu                   180      - #           185      - #           190                   - - Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gl - #y Leu Leu Asp Gln Arg               195          - #       200          - #       205                       - - Leu Ala Leu Gln Trp Val Gln Glu Asn Val Al - #a Ala Phe Gly Gly Asp           210              - #   215              - #   220                           - - Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Al - #a Gly Ala Ala Ser Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Met His Leu Leu Ser Pro Pro Ser Arg Gl - #y Leu Phe His Arg         Ala                                                                                              245  - #               250  - #               255              - - Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Tr - #p Ala Thr Val Gly Met                   260      - #           265      - #           270                   - - Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Al - #a His Leu Val Gly Cys               275          - #       280          - #       285                       - - Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Gl - #u Leu Val Ala Cys Leu           290              - #   295              - #   300                           - - Arg Thr Arg Pro Ala Gln Val Leu Val Asn Hi - #s Glu Trp His Val Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Va - #l Pro Val Val Asp         Gly                                                                                              325  - #               330  - #               335              - - Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Il - #e Asn Ala Gly Asp Phe                   340      - #           345      - #           350                   - - His Gly Leu Gln Val Leu Val Gly Val Val Ly - #s Asp Glu Gly Ser Tyr               355          - #       360          - #       365                       - - Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Ly - #s Asp Asn Glu Ser Leu           370              - #   375              - #   380                           - - Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Ar - #g Val Gly Val Pro Gln       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Ser Asp Leu Ala Ala Glu Ala Val Val Le - #u His Tyr Thr Asp         Trp                                                                                              405  - #               410  - #               415              - - Leu His Pro Glu Asp Pro Ala Arg Leu Arg Gl - #u Ala Leu Ser Asp Val                   420      - #           425      - #           430                   - - Val Gly Asp His Asn Val Val Cys Pro Val Al - #a Gln Leu Ala Gly Arg               435          - #       440          - #       445                       - - Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Ty - #r Val Phe Glu His Arg           450              - #   455              - #   460                           - - Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gl - #y Val Pro His Gly Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu As - #p Pro Ser Arg Asn         Tyr                                                                                              485  - #               490  - #               495              - - Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Le - #u Met Arg Tyr Trp Ala                   500      - #           505      - #           510                   - - Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pr - #o Arg Asp Pro Lys Ala               515          - #       520          - #       525                       - - Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gl - #n Gln Tyr Val Ser Leu           530              - #   535              - #   540                           - - Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Le - #u Arg Ala Gln Ala Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Le - #u Ser Ala Thr Asp         Thr                                                                                              565  - #               570  - #               575              - - Leu Asp Glu Ala Glu Arg Gln Trp Lys Ala Gl - #u Phe His Arg Trp Ser                   580      - #           585      - #           590                   - - Ser Tyr Met Val His Trp Lys Asn Gln Phe As - #p His Tyr Ser Lys Gln               595          - #       600          - #       605                       - - Asp Arg Cys Ser Asp Leu                                                       610                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:21:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 614 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:                          - - Met Arg Pro Pro Gln Cys Leu Leu His Thr Pr - #o Ser Leu Ala Ser Pro       1               5   - #                10  - #                15                - - Leu Leu Leu Leu Leu Leu Trp Leu Leu Gly Gl - #y Gly Val Gly Ala Glu                   20      - #            25      - #            30                    - - Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Va - #l Arg Gly Gly Arg Leu               35          - #        40          - #        45                        - - Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pr - #o Val Ser Ala Phe Leu           50              - #    55              - #    60                            - - Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pr - #o Arg Arg Phe Leu Pro       65                  - #70                  - #75                  - #80         - - Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Va - #l Asp Ala Thr Thr Phe                       85  - #                90  - #                95                - - Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Le - #u Tyr Pro Gly Phe Glu                   100      - #           105      - #           110                   - - Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Le - #u Ser Glu Asp Cys Leu               115          - #       120          - #       125                       - - Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pr - #o Thr Ser Pro Thr Pro           130              - #   135              - #   140                           - - Val Leu Val Trp Ile Tyr Gly Gly Gly Phe Ty - #r Ser Gly Ala Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gl - #n Ala Glu Arg Thr         Val                                                                                              165  - #               170  - #               175              - - Leu Val Ser Met Asn Tyr Arg Val Gly Ala Ph - #e Gly Phe Leu Ala Leu                   180      - #           185      - #           190                   - - Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gl - #y Leu Leu Asp Gln Arg               195          - #       200          - #       205                       - - Leu Ala Leu Gln Trp Val Gln Glu Asn Val Al - #a Ala Phe Gly Gly Asp           210              - #   215              - #   220                           - - Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Al - #a Gly Ala Ala Ser Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Met His Leu Leu Ser Pro Pro Ser Arg Gl - #y Leu Phe His Arg         Ala                                                                                              245  - #               250  - #               255              - - Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Tr - #p Ala Thr Val Gly Met                   260      - #           265      - #           270                   - - Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Al - #a His Leu Val Gly Cys               275          - #       280          - #       285                       - - Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Gl - #u Leu Val Ala Cys Leu           290              - #   295              - #   300                           - - Arg Thr Arg Pro Ala Gln Val Leu Val Asn Hi - #s Glu Trp His Val Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Pro Gln Glu Ser Val His Arg Phe Ser Phe Va - #l Pro Val Val Asp         Gly                                                                                              325  - #               330  - #               335              - - Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Il - #e Asn Ala Gly Asp Phe                   340      - #           345      - #           350                   - - His Gly Leu Gln Val Leu Val Gly Val Val Ly - #s Asp Glu Gly Ser Tyr               355          - #       360          - #       365                       - - Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Ly - #s Asp Asn Glu Ser Leu           370              - #   375              - #   380                           - - Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Ar - #g Val Gly Val Pro Gln       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Ser Asp Leu Ala Ala Glu Ala Val Val Le - #u His Tyr Thr Asp         Trp                                                                                              405  - #               410  - #               415              - - Leu His Pro Glu Asp Pro Ala Arg Leu Arg Gl - #u Ala Leu Ser Asp Val                   420      - #           425      - #           430                   - - Val Gly Asp His Asn Val Val Cys Pro Val Al - #a Gln Leu Ala Gly Arg               435          - #       440          - #       445                       - - Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Ty - #r Val Phe Glu His Arg           450              - #   455              - #   460                           - - Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gl - #y Val Pro His Gly Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu As - #p Pro Ser Arg Asn         Tyr                                                                                              485  - #               490  - #               495              - - Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Le - #u Met Arg Tyr Trp Ala                   500      - #           505      - #           510                   - - Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pr - #o Arg Asp Pro Lys Ala               515          - #       520          - #       525                       - - Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gl - #n Gln Tyr Val Ser Leu           530              - #   535              - #   540                           - - Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Le - #u Arg Ala Gln Ala Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Le - #u Ser Ala Thr Asp         Thr                                                                                              565  - #               570  - #               575              - - Leu Asp Glu Ala Glu Arg Gln Trp Lys Ala Gl - #u Phe His Arg Trp Ser                   580      - #           585      - #           590                   - - Ser Tyr Met Val His Trp Lys Asn Gln Phe As - #p His Tyr Ser Lys Gln               595          - #       600          - #       605                       - - Asp Arg Cys Ser Asp Leu                                                       610                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:22:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 614 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:                               - - Met Arg Pro Pro Gln Cys Leu Leu His Thr Pr - #o Ser Leu Ala Ser Pro       1               5   - #                10  - #                15                - - Leu Leu Leu Leu Leu Leu Trp Leu Leu Gly Gl - #y Gly Val Gly Ala Glu                   20      - #            25      - #            30                    - - Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Va - #l Arg Gly Gly Arg Leu               35          - #        40          - #        45                        - - Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pr - #o Val Ser Ala Phe Leu           50              - #    55              - #    60                            - - Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pr - #o Arg Arg Phe Leu Pro       65                  - #70                  - #75                  - #80         - - Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Va - #l Asp Ala Thr Thr Phe                       85  - #                90  - #                95                - - Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Le - #u Tyr Pro Gly Phe Glu                   100      - #           105      - #           110                   - - Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Le - #u Ser Glu Asp Cys Leu               115          - #       120          - #       125                       - - Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pr - #o Thr Ser Pro Thr Pro           130              - #   135              - #   140                           - - Val Leu Val Trp Ile Tyr Gly Gly Gly Phe Ty - #r Ser Gly Ala Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gl - #n Ala Glu Arg Thr         Val                                                                                              165  - #               170  - #               175              - - Leu Val Ser Met Asn Tyr Arg Val Gly Ala Ph - #e Gly Phe Leu Ala Leu                   180      - #           185      - #           190                   - - Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gl - #y Leu Leu Asp Gln Arg               195          - #       200          - #       205                       - - Leu Ala Leu Gln Trp Val Gln Glu Asn Val Al - #a Ala Phe Gly Gly Asp           210              - #   215              - #   220                           - - Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Al - #a Gly Ala Ala Ser Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Met His Leu Leu Ser Pro Pro Ser Arg Gl - #y Leu Phe His Arg         Ala                                                                                              245  - #               250  - #               255              - - Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Tr - #p Ala Thr Val Gly Met                   260      - #           265      - #           270                   - - Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Al - #a His Leu Val Gly Cys               275          - #       280          - #       285                       - - Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Gl - #u Leu Val Ala Cys Leu           290              - #   295              - #   300                           - - Arg Thr Arg Pro Ala Gln Val Leu Val Asn Hi - #s Glu Trp His Val Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Pro Gln Glu Ser Val His Arg Phe Ser Phe Va - #l Pro Val Val Asp         Gly                                                                                              325  - #               330  - #               335              - - Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Il - #e Asn Ala Gly Asp Phe                   340      - #           345      - #           350                   - - His Gly Leu Gln Val Leu Val Gly Val Val Ly - #s Asp Glu Gly Ser Tyr               355          - #       360          - #       365                       - - Asp Leu Val Tyr Gly Ala Pro Gly Phe Ser Ly - #s Asp Asn Glu Ser Leu           370              - #   375              - #   380                           - - Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Ar - #g Val Gly Val Pro Gln       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Ser Asp Leu Ala Ala Glu Ala Val Val Le - #u His Tyr Thr Asp         Trp                                                                                              405  - #               410  - #               415              - - Leu His Pro Glu Asp Pro Ala Arg Leu Arg Gl - #u Ala Leu Ser Asp Val                   420      - #           425      - #           430                   - - Val Gly Asp His Asn Val Val Cys Pro Val Al - #a Gln Leu Ala Gly Arg               435          - #       440          - #       445                       - - Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Ty - #r Val Phe Glu His Arg           450              - #   455              - #   460                           - - Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gl - #y Val Pro His Gly Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu As - #p Pro Ser Arg Asn         Tyr                                                                                              485  - #               490  - #               495              - - Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Le - #u Met Arg Tyr Trp Ala                   500      - #           505      - #           510                   - - Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pr - #o Arg Asp Pro Lys Ala               515          - #       520          - #       525                       - - Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gl - #n Gln Tyr Val Ser Leu           530              - #   535              - #   540                           - - Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Le - #u Arg Ala Gln Ala Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Le - #u Ser Ala Thr Asp         Thr                                                                                              565  - #               570  - #               575              - - Leu Asp Glu Ala Glu Arg Gln Trp Lys Ala Gl - #u Phe His Arg Trp Ser                   580      - #           585      - #           590                   - - Ser Tyr Met Val His Trp Lys Asn Gln Phe As - #p His Tyr Ser Lys Gln               595          - #       600          - #       605                       - - Asp Arg Cys Ser Asp Leu                                                       610                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:23:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 614 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:                               - - Met Arg Pro Pro Gln Cys Leu Leu His Thr Pr - #o Ser Leu Ala Ser Pro       1               5   - #                10  - #                15                - - Leu Leu Leu Leu Leu Leu Trp Leu Leu Gly Gl - #y Gly Val Gly Ala Glu                   20      - #            25      - #            30                    - - Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Va - #l Arg Gly Gly Arg Leu               35          - #        40          - #        45                        - - Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pr - #o Val Ser Ala Phe Leu           50              - #    55              - #    60                            - - Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pr - #o Arg Arg Phe Leu Pro       65                  - #70                  - #75                  - #80         - - Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Va - #l Asp Ala Thr Thr Phe                       85  - #                90  - #                95                - - Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Le - #u Tyr Pro Gly Phe Glu                   100      - #           105      - #           110                   - - Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Le - #u Ser Glu Asp Cys Leu               115          - #       120          - #       125                       - - Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pr - #o Thr Ser Pro Thr Pro           130              - #   135              - #   140                           - - Val Leu Val Trp Ile Tyr Gly Gly Gly Phe Ty - #r Ser Gly Ala Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gl - #n Ala Glu Arg Thr         Val                                                                                              165  - #               170  - #               175              - - Leu Val Ser Met Asn Tyr Arg Val Gly Ala Ph - #e Gly Phe Leu Ala Leu                   180      - #           185      - #           190                   - - Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gl - #y Leu Leu Asp Gln Arg               195          - #       200          - #       205                       - - Leu Ala Leu Gln Trp Val Gln Glu Asn Val Al - #a Ala Phe Gly Gly Asp           210              - #   215              - #   220                           - - Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Al - #a Gly Ala Ala Ser Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Met His Leu Leu Ser Pro Pro Ser Arg Gl - #y Leu Phe His Arg         Ala                                                                                              245  - #               250  - #               255              - - Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Tr - #p Ala Thr Val Gly Met                   260      - #           265      - #           270                   - - Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Al - #a His Leu Val Gly Cys               275          - #       280          - #       285                       - - Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Gl - #u Leu Val Ala Cys Leu           290              - #   295              - #   300                           - - Arg Thr Arg Pro Ala Gln Val Leu Val Asn Hi - #s Glu Trp His Val Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Pro Gln Glu Ser Val His Arg Phe Ser Phe Va - #l Pro Val Val Asp         Gly                                                                                              325  - #               330  - #               335              - - Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Il - #e Asn Ala Gly Asp Phe                   340      - #           345      - #           350                   - - His Gly Leu Gln Val Leu Val Gly Val Val Ly - #s Asp Glu Gly Ser Tyr               355          - #       360          - #       365                       - - Glu Leu Val Tyr Gly Ala Pro Gly Phe Ser Ly - #s Asp Asn Glu Ser Leu           370              - #   375              - #   380                           - - Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Ar - #g Val Gly Val Pro Gln       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Ser Asp Leu Ala Ala Glu Ala Val Val Le - #u His Tyr Thr Asp         Trp                                                                                              405  - #               410  - #               415              - - Leu His Pro Glu Asp Pro Ala Arg Leu Arg Gl - #u Ala Leu Ser Asp Val                   420      - #           425      - #           430                   - - Val Gly Asp His Asn Val Val Cys Pro Val Al - #a Gln Leu Ala Gly Arg               435          - #       440          - #       445                       - - Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Ty - #r Val Phe Glu His Arg           450              - #   455              - #   460                           - - Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gl - #y Val Pro His Gly Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu As - #p Pro Ser Arg Asn         Tyr                                                                                              485  - #               490  - #               495              - - Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Le - #u Met Arg Tyr Trp Ala                   500      - #           505      - #           510                   - - Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pr - #o Arg Asp Pro Lys Ala               515          - #       520          - #       525                       - - Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gl - #n Gln Tyr Val Ser Leu           530              - #   535              - #   540                           - - Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Le - #u Arg Ala Gln Ala Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Le - #u Ser Ala Thr Asp         Thr                                                                                              565  - #               570  - #               575              - - Leu Asp Glu Ala Glu Arg Gln Trp Lys Ala Gl - #u Phe His Arg Trp Ser                   580      - #           585      - #           590                   - - Ser Tyr Met Val His Trp Lys Asn Gln Phe As - #p His Tyr Ser Lys Gln               595          - #       600          - #       605                       - - Asp Arg Cys Ser Asp Leu                                                       610                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:24:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 602 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:                               - - Met His Ser Lys Val Thr Ile Ile Cys Ile Ar - #g Phe Leu Phe Trp Phe       1               5   - #                10  - #                15                - - Leu Leu Leu Cys Met Leu Ile Gly Lys Ser Hi - #s Thr Glu Asp Asp Ile                   20      - #            25      - #            30                    - - Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gl - #y Met Asn Leu Thr Val               35          - #        40          - #        45                        - - Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Il - #e Pro Tyr Ala Gln Pro           50              - #    55              - #    60                            - - Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gl - #n Ser Leu Thr Lys Trp       65                  - #70                  - #75                  - #80         - - Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala As - #n Ser Cys Cys Gln Asn                       85  - #                90  - #                95                - - Ile Asp Gln Ser Phe Pro Gly Phe His Gly Se - #r Glu Met Trp Asn Pro                   100      - #           105      - #           110                   - - Asn Thr Asp Leu Ser Glu Asp Cys Leu Tyr Le - #u Asn Val Trp Ile Pro               115          - #       120          - #       125                       - - Ala Pro Lys Pro Lys Asn Ala Thr Val Leu Il - #e Trp Ile Tyr Gly Gly           130              - #   135              - #   140                           - - Gly Phe Gln Thr Gly Thr Ser Ser Leu His Va - #l Tyr Asp Gly Lys Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Ala Arg Val Glu Arg Val Ile Val Val Se - #r Met Asn Tyr Arg         Val                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Gly Phe Leu Ala Leu Pro Gly As - #n Pro Glu Ala Pro Gly                   180      - #           185      - #           190                   - - Asn Met Gly Leu Phe Asp Gln Gln Leu Ala Le - #u Gln Trp Val Gln Lys               195          - #       200          - #       205                       - - Asn Ile Ala Ala Phe Gly Gly Asn Pro Lys Se - #r Val Thr Leu Phe Gly           210              - #   215              - #   220                           - - Glu Ser Ala Gly Ala Ala Ser Val Ser Leu Hi - #s Leu Leu Ser Pro Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gl - #n Ser Gly Ser Phe         Asn                                                                                              245  - #               250  - #               255              - - Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Al - #a Arg Asn Arg Thr Leu                   260      - #           265      - #           270                   - - Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Gl - #u Asn Glu Thr Glu Ile               275          - #       280          - #       285                       - - Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Gl - #u Ile Leu Leu Asn Glu           290              - #   295              - #   300                           - - Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Se - #r Val Asn Phe Gly Pro       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Val Asp Gly Asp Phe Leu Thr Asp Met Pr - #o Asp Ile Leu Leu         Glu                                                                                              325  - #               330  - #               335              - - Leu Gly Gln Phe Lys Lys Thr Gln Ile Leu Va - #l Gly Val Asn Lys Asp                   340      - #           345      - #           350                   - - Glu Gly Thr Ala Phe Leu Val Tyr Gly Ala Pr - #o Gly Phe Ser Lys Asp               355          - #       360          - #       365                       - - Asn Asn Ser Ile Ile Thr Arg Lys Glu Phe Gl - #n Glu Gly Leu Lys Ile           370              - #   375              - #   380                           - - Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Gl - #u Ser Ile Leu Phe His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Tyr Thr Asp Trp Val Asp Asp Gln Arg Pro Gl - #u Asn Tyr Arg Glu         Ala                                                                                              405  - #               410  - #               415              - - Leu Gly Asp Val Val Gly Asp Tyr Asn Phe Il - #e Cys Pro Ala Leu Glu                   420      - #           425      - #           430                   - - Phe Thr Lys Lys Phe Ser Glu Trp Gly Asn As - #n Ala Phe Phe Tyr Tyr               435          - #       440          - #       445                       - - Phe Glu His Arg Ser Ser Lys Leu Pro Trp Pr - #o Glu Trp Met Gly Val           450              - #   455              - #   460                           - - Met His Gly Tyr Glu Ile Glu Phe Val Phe Gl - #y Leu Pro Leu Glu Arg       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Le - #u Ser Arg Ser Ile         Val                                                                                              485  - #               490  - #               495              - - Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly As - #n Pro Asn Glu Thr Gln                   500      - #           505      - #           510                   - - Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Se - #r Thr Glu Gln Lys Tyr               515          - #       520          - #       525                       - - Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Me - #t Thr Lys Leu Arg Ala           530              - #   535              - #   540                           - - Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pr - #o Lys Val Leu Glu Met       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu Tr - #p Lys Ala Gly Phe         His                                                                                              565  - #               570  - #               575              - - Arg Trp Asn Asn Tyr Met Met Asp Trp Lys As - #n Gln Phe Asn Asp Tyr                   580      - #           585      - #           590                   - - Thr Ser Lys Lys Glu Ser Cys Val Gly Leu                                           595          - #       600                                              - -  - - NFORMATION FOR SEQ ID NO:25:                                          - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 614 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:                               - - Met Arg Pro Pro Gln Cys Leu Leu His Thr Pr - #o Ser Leu Ala Ser Pro       1               5   - #                10  - #                15                - - Leu Leu Leu Leu Leu Leu Trp Leu Leu Gly Gl - #y Gly Val Gly Ala Glu                   20      - #            25      - #            30                    - - Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Va - #l Arg Gly Gly Arg Leu               35          - #        40          - #        45                        - - Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pr - #o Val Ser Ala Phe Leu           50              - #    55              - #    60                            - - Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pr - #o Arg Arg Phe Leu Pro       65                  - #70                  - #75                  - #80         - - Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Va - #l Asp Ala Thr Thr Phe                       85  - #                90  - #                95                - - Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Le - #u Tyr Pro Gly Phe Glu                   100      - #           105      - #           110                   - - Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Le - #u Ser Glu Asp Cys Leu               115          - #       120          - #       125                       - - Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pr - #o Thr Ser Pro Thr Pro           130              - #   135              - #   140                           - - Val Leu Val Trp Ile Tyr Gly Gly Gly Phe Hi - #s Ser Gly Ala Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gl - #n Ala Glu Arg Thr         Val                                                                                              165  - #               170  - #               175              - - Leu Val Ser Met Asn Tyr Arg Val Gly Ala Ph - #e Gly Phe Leu Ala Leu                   180      - #           185      - #           190                   - - Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gl - #y Leu Leu Asp Gln Arg               195          - #       200          - #       205                       - - Leu Ala Leu Gln Trp Val Gln Glu Asn Val Al - #a Ala Phe Gly Gly Asp           210              - #   215              - #   220                           - - Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Al - #a Gly Ala Ala Ser Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Met His Leu Leu Ser Pro Pro Ser Arg Gl - #y Leu Phe His Arg         Ala                                                                                              245  - #               250  - #               255              - - Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Tr - #p Ala Thr Val Gly Met                   260      - #           265      - #           270                   - - Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Al - #a His Leu Val Gly Cys               275          - #       280          - #       285                       - - Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Gl - #u Leu Val Ala Cys Leu           290              - #   295              - #   300                           - - Arg Thr Arg Pro Ala Gln Val Leu Val Asn Hi - #s Glu Trp His Val Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Va - #l Pro Val Val Asp         Gly                                                                                              325  - #               330  - #               335              - - Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Il - #e Asn Ala Gly Asp Phe                   340      - #           345      - #           350                   - - His Gly Leu Gln Val Leu Val Gly Val Val Ly - #s Asp Glu Gly Ser Tyr               355          - #       360          - #       365                       - - Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Ly - #s Asp Asn Glu Ser Leu           370              - #   375              - #   380                           - - Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Ar - #g Val Gly Val Pro Gln       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Ser Asp Leu Ala Ala Glu Ala Val Val Le - #u His Tyr Thr Asp         Trp                                                                                              405  - #               410  - #               415              - - Leu His Pro Glu Asp Pro Ala Arg Leu Arg Gl - #u Ala Leu Ser Asp Val                   420      - #           425      - #           430                   - - Val Gly Asp His Asn Val Val Cys Pro Val Al - #a Gln Leu Ala Gly Arg               435          - #       440          - #       445                       - - Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Ty - #r Val Phe Glu His Arg           450              - #   455              - #   460                           - - Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gl - #y Val Pro His Gly Tyr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu As - #p Pro Ser Arg Asn         Tyr                                                                                              485  - #               490  - #               495              - - Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Le - #u Met Arg Tyr Trp Ala                   500      - #           505      - #           510                   - - Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pr - #o Arg Asp Pro Lys Ala               515          - #       520          - #       525                       - - Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gl - #n Gln Tyr Val Ser Leu           530              - #   535              - #   540                           - - Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Le - #u Arg Ala Gln Ala Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Le - #u Ser Ala Thr Asp         Thr                                                                                              565  - #               570  - #               575              - - Leu Asp Glu Ala Glu Arg Gln Trp Lys Ala Gl - #u Phe His Arg Trp Ser                   580      - #           585      - #           590                   - - Ser Tyr Met Val His Trp Lys Asn Gln Phe As - #p His Tyr Ser Lys Gln               595          - #       600          - #       605                       - - Asp Arg Cys Ser Asp Leu                                                       610                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:26:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 454 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:                               - - Glu His Cys Leu Tyr Leu Asn Ile Tyr Thr Pr - #o Ala Asp Leu Thr Lys       1               5   - #                10  - #                15                - - Lys Asn Arg Leu Pro Val Met Val Trp Ile Hi - #s Gly Gly Gly Leu Met                   20      - #            25      - #            30                    - - Val Gly Ala Ala Ser Thr Tyr Asp Gly Leu Al - #a Leu Ala Ala His Glu               35          - #        40          - #        45                        - - Asn Val Val Val Val Thr Ile Gln Tyr Arg Le - #u Gly Ile Trp Gly Phe           50              - #    55              - #    60                            - - Phe Ser Thr Gly Asp Glu His Ser Arg Gly As - #n Trp Gly His Leu Asp       65                  - #70                  - #75                  - #80         - - Gln Val Ala Ala Leu Arg Trp Val Gln Asp As - #n Ile Ala Ser Phe Gly                       85  - #                90  - #                95                - - Gly Asn Pro Gly Ser Val Thr Ile Phe Gly Gl - #u Ser Ala Gly Gly Glu                   100      - #           105      - #           110                   - - Ser Val Ser Val Leu Val Leu Ser Pro Leu Al - #a Lys Asn Leu Phe His               115          - #       120          - #       125                       - - Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Th - #r Ser Val Leu Val Lys           130              - #   135              - #   140                           - - Lys Gly Asp Val Lys Pro Leu Ala Glu Gln Il - #e Ala Ile Thr Ala Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Cys Lys Thr Thr Thr Ser Ala Ala Met Val Hi - #s Cys Leu Arg Gln         Lys                                                                                              165  - #               170  - #               175              - - Thr Glu Glu Glu Leu Leu Glu Thr Thr Leu Ly - #s Ile Gly Asn Ser Tyr                   180      - #           185      - #           190                   - - Leu Trp Thr Tyr Arg Glu Thr Gln Arg Glu Se - #r Thr Leu Leu Gly Thr               195          - #       200          - #       205                       - - Val Ile Asp Gly Met Leu Leu Leu Lys Thr Pr - #o Glu Glu Leu Gln Arg           210              - #   215              - #   220                           - - Glu Arg Asn Phe His Thr Val Pro Tyr Met Va - #l Gly Ile Asn Lys Gln       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Phe Gly Trp Leu Ile Pro Met Gln Leu Me - #t Ser Tyr Pro Leu         Ser                                                                                              245  - #               250  - #               255              - - Glu Gly Gln Leu Asp Gln Lys Thr Ala Met Se - #r Leu Leu Gly Ser Pro                   260      - #           265      - #           270                   - - Ile Pro Leu Phe Ala Ile Ala Lys Glu Leu Il - #e Pro Glu Ala Thr Glu               275          - #       280          - #       285                       - - Lys Tyr Leu Gly Gly Thr Asp Asp Thr Val Ly - #s Lys Lys Asp Leu Ile           290              - #   295              - #   300                           - - Leu Asp Leu Ile Ala Asp Val Met Phe Gly Va - #l Pro Ser Val Ile Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Arg Asn His Arg Asp Ala Gly Ala Pro Th - #r Tyr Met Tyr Glu         Phe                                                                                              325  - #               330  - #               335              - - Gln Tyr Arg Pro Ser Phe Ser Ser Asp Met Ly - #s Pro Lys Thr Val Ile                   340      - #           345      - #           350                   - - Gly Asp His Gly Asp Glu Leu Phe Ser Val Ph - #e Gly Ala Pro Phe Leu               355          - #       360          - #       365                       - - Lys Glu Gly Ala Ser Glu Glu Glu Ile Arg Le - #u Ser Lys Met Val Met           370              - #   375              - #   380                           - - Lys Phe Trp Ala Asn Phe Ala Arg Asn Gly As - #n Pro Asn Gly Lys Gly       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Pro His Trp Pro Glu Tyr Asn Gln Lys Gl - #u Gly Tyr Leu Gln         Ile                                                                                              405  - #               410  - #               415              - - Gly Ala Asn Thr Gln Ala Ala Gln Lys Leu Ly - #s Asp Lys Glu Val Ala                   420      - #           425      - #           430                   - - Phe Trp Thr Asn Leu Phe Ala Lys Lys Ala Va - #l Glu Lys Pro Pro Gln               435          - #       440          - #       445                       - - Thr Asp His Ile Glu Leu                                                       450                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:27:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 454 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:                               - - Glu His Cys Leu Tyr Leu Asn Ile Tyr Thr Pr - #o Ala Asp Leu Thr Lys       1               5   - #                10  - #                15                - - Lys Asn Arg Leu Pro Val Met Val Trp Ile Hi - #s Gly Gly His Leu Met                   20      - #            25      - #            30                    - - Val Gly Ala Ala Ser Thr Tyr Asp Gly Leu Al - #a Leu Ala Ala His Glu               35          - #        40          - #        45                        - - Asn Val Val Val Val Thr Ile Gln Tyr Arg Le - #u Gly Ile Trp Gly Phe           50              - #    55              - #    60                            - - Phe Ser Thr Gly Asp Glu His Ser Arg Gly As - #n Trp Gly His Leu Asp       65                  - #70                  - #75                  - #80         - - Gln Val Ala Ala Leu Arg Trp Val Gln Asp As - #n Ile Ala Ser Phe Gly                       85  - #                90  - #                95                - - Gly Asn Pro Gly Ser Val Thr Ile Phe Gly Gl - #u Ser Ala Gly Gly Glu                   100      - #           105      - #           110                   - - Ser Val Ser Val Leu Val Leu Ser Pro Leu Al - #a Lys Asn Leu Phe His               115          - #       120          - #       125                       - - Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Th - #r Ser Val Leu Val Lys           130              - #   135              - #   140                           - - Lys Gly Asp Val Lys Pro Leu Ala Glu Gln Il - #e Ala Ile Thr Ala Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Cys Lys Thr Thr Thr Ser Ala Ala Met Val Hi - #s Cys Leu Arg Gln         Lys                                                                                              165  - #               170  - #               175              - - Thr Glu Glu Glu Leu Leu Glu Thr Thr Leu Ly - #s Ile Gly Asn Ser Tyr                   180      - #           185      - #           190                   - - Leu Trp Thr Tyr Arg Glu Thr Gln Arg Glu Se - #r Thr Leu Leu Gly Thr               195          - #       200          - #       205                       - - Val Ile Asp Gly Met Leu Leu Leu Lys Thr Pr - #o Glu Glu Leu Gln Arg           210              - #   215              - #   220                           - - Glu Arg Asn Phe His Thr Val Pro Tyr Met Va - #l Gly Ile Asn Lys Gln       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Phe Gly Trp Leu Ile Pro Met Gln Leu Me - #t Ser Tyr Pro Leu         Ser                                                                                              245  - #               250  - #               255              - - Glu Gly Gln Leu Asp Gln Lys Thr Ala Met Se - #r Leu Leu Gly Ser Pro                   260      - #           265      - #           270                   - - Ile Pro Leu Phe Ala Ile Ala Lys Glu Leu Il - #e Pro Glu Ala Thr Glu               275          - #       280          - #       285                       - - Lys Tyr Leu Gly Gly Thr Asp Asp Thr Val Ly - #s Lys Lys Asp Leu Ile           290              - #   295              - #   300                           - - Leu Asp Leu Ile Ala Asp Val Met Phe Gly Va - #l Pro Ser Val Ile Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Arg Asn His Arg Asp Ala Gly Ala Pro Th - #r Tyr Met Tyr Glu         Phe                                                                                              325  - #               330  - #               335              - - Gln Tyr Arg Pro Ser Phe Ser Ser Asp Met Ly - #s Pro Lys Thr Val Ile                   340      - #           345      - #           350                   - - Gly Asp His Gly Asp Glu Leu Phe Ser Val Ph - #e Gly Ala Pro Phe Leu               355          - #       360          - #       365                       - - Lys Glu Gly Ala Ser Glu Glu Glu Ile Arg Le - #u Ser Lys Met Val Met           370              - #   375              - #   380                           - - Lys Phe Trp Ala Asn Phe Ala Arg Asn Gly As - #n Pro Asn Gly Lys Gly       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Pro His Trp Pro Glu Tyr Asn Gln Lys Gl - #u Gly Tyr Leu Gln         Ile                                                                                              405  - #               410  - #               415              - - Gly Ala Asn Thr Gln Ala Ala Gln Lys Leu Ly - #s Asp Lys Glu Val Ala                   420      - #           425      - #           430                   - - Phe Trp Thr Asn Leu Phe Ala Lys Lys Ala Va - #l Glu Lys Pro Pro Gln               435          - #       440          - #       445                       - - Thr Asp His Ile Glu Leu                                                       450                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:28:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 454 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:                               - - Glu His Cys Leu Tyr Leu Asn Ile Tyr Thr Pr - #o Ala Asp Leu Thr Lys       1               5   - #                10  - #                15                - - Lys Asn Arg Leu Pro Val Met Val Trp Ile Hi - #s Gly Gly His Leu Glu                   20      - #            25      - #            30                    - - Val Gly Ala Ala Ser Thr Tyr Asp Gly Leu Al - #a Leu Ala Ala His Glu               35          - #        40          - #        45                        - - Asn Val Val Val Val Thr Ile Gln Tyr Arg Le - #u Gly Ile Trp Gly Phe           50              - #    55              - #    60                            - - Phe Ser Thr Gly Asp Glu His Ser Arg Gly As - #n Trp Gly His Leu Asp       65                  - #70                  - #75                  - #80         - - Gln Val Ala Ala Leu Arg Trp Val Gln Asp As - #n Ile Ala Ser Phe Gly                       85  - #                90  - #                95                - - Gly Asn Pro Gly Ser Val Thr Ile Phe Gly Gl - #u Ser Ala Gly Gly Glu                   100      - #           105      - #           110                   - - Ser Val Ser Val Leu Val Leu Ser Pro Leu Al - #a Lys Asn Leu Phe His               115          - #       120          - #       125                       - - Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Th - #r Ser Val Leu Val Lys           130              - #   135              - #   140                           - - Lys Gly Asp Val Lys Pro Leu Ala Glu Gln Il - #e Ala Ile Thr Ala Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Cys Lys Thr Thr Thr Ser Ala Ala Met Val Hi - #s Cys Leu Arg Gln         Lys                                                                                              165  - #               170  - #               175              - - Thr Glu Glu Glu Leu Leu Glu Thr Thr Leu Ly - #s Ile Gly Asn Ser Tyr                   180      - #           185      - #           190                   - - Leu Trp Thr Tyr Arg Glu Thr Gln Arg Glu Se - #r Thr Leu Leu Gly Thr               195          - #       200          - #       205                       - - Val Ile Asp Gly Met Leu Leu Leu Lys Thr Pr - #o Glu Glu Leu Gln Arg           210              - #   215              - #   220                           - - Glu Arg Asn Phe His Thr Val Pro Tyr Met Va - #l Gly Ile Asn Lys Gln       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Phe Gly Trp Leu Ile Pro Met Gln Leu Me - #t Ser Tyr Pro Leu         Ser                                                                                              245  - #               250  - #               255              - - Glu Gly Gln Leu Asp Gln Lys Thr Ala Met Se - #r Leu Leu Gly Ser Pro                   260      - #           265      - #           270                   - - Ile Pro Leu Phe Ala Ile Ala Lys Glu Leu Il - #e Pro Glu Ala Thr Glu               275          - #       280          - #       285                       - - Lys Tyr Leu Gly Gly Thr Asp Asp Thr Val Ly - #s Lys Lys Asp Leu Ile           290              - #   295              - #   300                           - - Leu Asp Leu Ile Ala Asp Val Met Phe Gly Va - #l Pro Ser Val Ile Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Arg Asn His Arg Asp Ala Gly Ala Pro Th - #r Tyr Met Tyr Glu         Phe                                                                                              325  - #               330  - #               335              - - Gln Tyr Arg Pro Ser Phe Ser Ser Asp Met Ly - #s Pro Lys Thr Val Ile                   340      - #           345      - #           350                   - - Gly Asp His Gly Asp Glu Leu Phe Ser Val Ph - #e Gly Ala Pro Phe Leu               355          - #       360          - #       365                       - - Lys Glu Gly Ala Ser Glu Glu Glu Ile Arg Le - #u Ser Lys Met Val Met           370              - #   375              - #   380                           - - Lys Phe Trp Ala Asn Phe Ala Arg Asn Gly As - #n Pro Asn Gly Lys Gly       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Pro His Trp Pro Glu Tyr Asn Gln Lys Gl - #u Gly Tyr Leu Gln         Ile                                                                                              405  - #               410  - #               415              - - Gly Ala Asn Thr Gln Ala Ala Gln Lys Leu Ly - #s Asp Lys Glu Val Ala                   420      - #           425      - #           430                   - - Phe Trp Thr Asn Leu Phe Ala Lys Lys Ala Va - #l Glu Lys Pro Pro Gln               435          - #       440          - #       445                       - - Thr Asp His Ile Glu Leu                                                       450                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:29:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 454 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:                               - - Glu His Cys Leu Tyr Leu Asn Ile Tyr Thr Pr - #o Ala Asp Leu Thr Lys       1               5   - #                10  - #                15                - - Lys Asn Arg Leu Pro Val Met Val Trp Ile Hi - #s Gly Gly His Leu Asp                   20      - #            25      - #            30                    - - Val Gly Ala Ala Ser Thr Tyr Asp Gly Leu Al - #a Leu Ala Ala His Glu               35          - #        40          - #        45                        - - Asn Val Val Val Val Thr Ile Gln Tyr Arg Le - #u Gly Ile Trp Gly Phe           50              - #    55              - #    60                            - - Phe Ser Thr Gly Asp Glu His Ser Arg Gly As - #n Trp Gly His Leu Asp       65                  - #70                  - #75                  - #80         - - Gln Val Ala Ala Leu Arg Trp Val Gln Asp As - #n Ile Ala Ser Phe Gly                       85  - #                90  - #                95                - - Gly Asn Pro Gly Ser Val Thr Ile Phe Gly Gl - #u Ser Ala Gly Gly Glu                   100      - #           105      - #           110                   - - Ser Val Ser Val Leu Val Leu Ser Pro Leu Al - #a Lys Asn Leu Phe His               115          - #       120          - #       125                       - - Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Th - #r Ser Val Leu Val Lys           130              - #   135              - #   140                           - - Lys Gly Asp Val Lys Pro Leu Ala Glu Gln Il - #e Ala Ile Thr Ala Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Cys Lys Thr Thr Thr Ser Ala Ala Met Val Hi - #s Cys Leu Arg Gln         Lys                                                                                              165  - #               170  - #               175              - - Thr Glu Glu Glu Leu Leu Glu Thr Thr Leu Ly - #s Ile Gly Asn Ser Tyr                   180      - #           185      - #           190                   - - Leu Trp Thr Tyr Arg Glu Thr Gln Arg Glu Se - #r Thr Leu Leu Gly Thr               195          - #       200          - #       205                       - - Val Ile Asp Gly Met Leu Leu Leu Lys Thr Pr - #o Glu Glu Leu Gln Arg           210              - #   215              - #   220                           - - Glu Arg Asn Phe His Thr Val Pro Tyr Met Va - #l Gly Ile Asn Lys Gln       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Phe Gly Trp Leu Ile Pro Met Gln Leu Me - #t Ser Tyr Pro Leu         Ser                                                                                              245  - #               250  - #               255              - - Glu Gly Gln Leu Asp Gln Lys Thr Ala Met Se - #r Leu Leu Gly Ser Pro                   260      - #           265      - #           270                   - - Ile Pro Leu Phe Ala Ile Ala Lys Glu Leu Il - #e Pro Glu Ala Thr Glu               275          - #       280          - #       285                       - - Lys Tyr Leu Gly Gly Thr Asp Asp Thr Val Ly - #s Lys Lys Asp Leu Ile           290              - #   295              - #   300                           - - Leu Asp Leu Ile Ala Asp Val Met Phe Gly Va - #l Pro Ser Val Ile Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Arg Asn His Arg Asp Ala Gly Ala Pro Th - #r Tyr Met Tyr Glu         Phe                                                                                              325  - #               330  - #               335              - - Gln Tyr Arg Pro Ser Phe Ser Ser Asp Met Ly - #s Pro Lys Thr Val Ile                   340      - #           345      - #           350                   - - Gly Asp His Gly Asp Glu Leu Phe Ser Val Ph - #e Gly Ala Pro Phe Leu               355          - #       360          - #       365                       - - Lys Glu Gly Ala Ser Glu Glu Glu Ile Arg Le - #u Ser Lys Met Val Met           370              - #   375              - #   380                           - - Lys Phe Trp Ala Asn Phe Ala Arg Asn Gly As - #n Pro Asn Gly Lys Gly       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Pro His Trp Pro Glu Tyr Asn Gln Lys Gl - #u Gly Tyr Leu Gln         Ile                                                                                              405  - #               410  - #               415              - - Gly Ala Asn Thr Gln Ala Ala Gln Lys Leu Ly - #s Asp Lys Glu Val Ala                   420      - #           425      - #           430                   - - Phe Trp Thr Asn Leu Phe Ala Lys Lys Ala Va - #l Glu Lys Pro Pro Gln               435          - #       440          - #       445                       - - Thr Asp His Ile Glu Leu                                                       450                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:30:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 454 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:                               - - Glu His Cys Leu Tyr Leu Asn Ile Tyr Thr Pr - #o Ala Asp Leu Thr Lys       1               5   - #                10  - #                15                - - Lys Asn Arg Leu Pro Val Met Val Trp Ile Hi - #s Gly Gly Gly Leu Met                   20      - #            25      - #            30                    - - Val Gly Ala Ala Ser Thr Tyr Asp Gly Leu Al - #a Leu Ala Ala His Glu               35          - #        40          - #        45                        - - Asn Val Val Val Val Thr Ile Gln Tyr Arg Le - #u Gly Ile Trp Gly Phe           50              - #    55              - #    60                            - - Phe Ser Thr Gly Asp Glu His Ser Arg Gly As - #n Trp Gly His Leu Asp       65                  - #70                  - #75                  - #80         - - Gln Val Ala Ala Leu Arg Trp Val Gln Asp As - #n Ile Ala Ser Phe Gly                       85  - #                90  - #                95                - - Gly Asn Pro Gly Ser Val Thr Ile Phe Gly Gl - #u Ser Ala Gly Gly Glu                   100      - #           105      - #           110                   - - Ser Val Ser Val Leu Val Leu Ser Pro Leu Al - #a Lys Asn Leu Phe His               115          - #       120          - #       125                       - - Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Th - #r Ser Val Leu Val Lys           130              - #   135              - #   140                           - - Lys Gly Asp Val Lys Pro Leu Ala Glu Gln Il - #e Ala Ile Thr Ala Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Cys Lys Thr Thr Thr Ser Ala Ala Met Val Hi - #s Cys Leu Arg Gln         Lys                                                                                              165  - #               170  - #               175              - - Thr Glu Glu Glu Leu Leu Glu Thr Thr Leu Ly - #s Ile Gly Asn Ser Tyr                   180      - #           185      - #           190                   - - Leu Trp Thr Tyr Arg Glu Thr Gln Arg His Se - #r Thr Leu Leu Gly Thr               195          - #       200          - #       205                       - - Val Ile Asp Gly Met Leu Leu Leu Lys Thr Pr - #o Glu Glu Leu Gln Arg           210              - #   215              - #   220                           - - Glu Arg Asn Phe His Thr Val Pro Tyr Met Va - #l Gly Ile Asn Lys Gln       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Phe Gly Trp Leu Ile Pro Met Gln Leu Me - #t Ser Tyr Pro Leu         Ser                                                                                              245  - #               250  - #               255              - - Glu Gly Gln Leu Asp Gln Lys Thr Ala Met Se - #r Leu Leu Gly Ser Pro                   260      - #           265      - #           270                   - - Ile Pro Leu Phe Ala Ile Ala Lys Glu Leu Il - #e Pro Glu Ala Thr Glu               275          - #       280          - #       285                       - - Lys Tyr Leu Gly Gly Thr Asp Asp Thr Val Ly - #s Lys Lys Asp Leu Ile           290              - #   295              - #   300                           - - Leu Asp Leu Ile Ala Asp Val Met Phe Gly Va - #l Pro Ser Val Ile Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Arg Asn His Arg Asp Ala Gly Ala Pro Th - #r Tyr Met Tyr Glu         Phe                                                                                              325  - #               330  - #               335              - - Gln Tyr Arg Pro Ser Phe Ser Ser Asp Met Ly - #s Pro Lys Thr Val Ile                   340      - #           345      - #           350                   - - Gly Asp His Gly Asp Glu Leu Phe Ser Val Ph - #e Gly Ala Pro Phe Leu               355          - #       360          - #       365                       - - Lys Glu Gly Ala Ser Glu Glu Glu Ile Arg Le - #u Ser Lys Met Val Met           370              - #   375              - #   380                           - - Lys Phe Trp Ala Asn Phe Ala Arg Asn Gly As - #n Pro Asn Gly Lys Gly       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Pro His Trp Pro Glu Tyr Asn Gln Lys Gl - #u Gly Tyr Leu Gln         Ile                                                                                              405  - #               410  - #               415              - - Gly Ala Asn Thr Gln Ala Ala Gln Lys Leu Ly - #s Asp Lys Glu Val Ala                   420      - #           425      - #           430                   - - Phe Trp Thr Asn Leu Phe Ala Lys Lys Ala Va - #l Glu Lys Pro Pro Gln               435          - #       440          - #       445                       - - Thr Asp His Ile Glu Leu                                                       450                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:31:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 454 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: unknown                                                 - -     (ii) MOLECULE TYPE: protein                                            - -    (iii) HYPOTHETICAL: YES                                                 - -     (iv) ANTI-SENSE: YES                                                   - -      (v) FRAGMENT TYPE: N-terminal                                         - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM: human est - #erases                                     - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:                               - - Glu His Cys Leu Tyr Leu Asn Ile Tyr Thr Pr - #o Ala Asp Leu Thr Lys       1               5   - #                10  - #                15                - - Lys Asn Arg Leu Pro Val Met Val Trp Ile Hi - #s Gly Gly Gly Leu Met                   20      - #            25      - #            30                    - - Val Gly Ala Ala Ser Thr Tyr Asp Gly Leu Al - #a Leu Ala Ala His Glu               35          - #        40          - #        45                        - - Asn Val Val Val Val Thr Ile Gln Tyr Arg Le - #u Gly Ile Trp Gly Phe           50              - #    55              - #    60                            - - Phe Ser Thr Gly Asp Glu His Ser Arg Gly As - #n Trp Gly His Leu Asp       65                  - #70                  - #75                  - #80         - - Gln Val Ala Ala Leu Arg Trp Val Gln Asp As - #n Ile Ala Ser Phe Gly                       85  - #                90  - #                95                - - Gly Asn Pro Gly Ser Val Thr Ile Phe Gly Gl - #u Ser Ala Gly Gly Glu                   100      - #           105      - #           110                   - - Ser Val Ser Val Leu Val Leu Ser Pro Leu Al - #a Lys Asn Leu Phe His               115          - #       120          - #       125                       - - Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Th - #r Ser Val Leu Val Lys           130              - #   135              - #   140                           - - Lys Gly Asp Val Lys Pro Leu Ala Glu Gln Il - #e Ala Ile Thr Ala Gly       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Cys Lys Thr Thr Thr Ser Ala Ala Met Val Hi - #s Cys Leu Arg Gln         Lys                                                                                              165  - #               170  - #               175              - - Thr Glu Glu Glu Leu Leu Glu Thr Thr Leu Ly - #s Ile Gly Asn Ser Tyr                   180      - #           185      - #           190                   - - Leu Trp Thr Tyr Arg Glu Thr Gln Arg Glu Se - #r His Leu Leu Gly Thr               195          - #       200          - #       205                       - - Val Ile Asp Gly Met Leu Leu Leu Lys Thr Pr - #o Glu Glu Leu Gln Arg           210              - #   215              - #   220                           - - Glu Arg Asn Phe His Thr Val Pro Tyr Met Va - #l Gly Ile Asn Lys Gln       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Phe Gly Trp Leu Ile Pro Met Gln Leu Me - #t Ser Tyr Pro Leu         Ser                                                                                              245  - #               250  - #               255              - - Glu Gly Gln Leu Asp Gln Lys Thr Ala Met Se - #r Leu Leu Gly Ser Pro                   260      - #           265      - #           270                   - - Ile Pro Leu Phe Ala Ile Ala Lys Glu Leu Il - #e Pro Glu Ala Thr Glu               275          - #       280          - #       285                       - - Lys Tyr Leu Gly Gly Thr Asp Asp Thr Val Ly - #s Lys Lys Asp Leu Ile           290              - #   295              - #   300                           - - Leu Asp Leu Ile Ala Asp Val Met Phe Gly Va - #l Pro Ser Val Ile Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ala Arg Asn His Arg Asp Ala Gly Ala Pro Th - #r Tyr Met Tyr Glu         Phe                                                                                              325  - #               330  - #               335              - - Gln Tyr Arg Pro Ser Phe Ser Ser Asp Met Ly - #s Pro Lys Thr Val Ile                   340      - #           345      - #           350                   - - Gly Asp His Gly Asp Glu Leu Phe Ser Val Ph - #e Gly Ala Pro Phe Leu               355          - #       360          - #       365                       - - Lys Glu Gly Ala Ser Glu Glu Glu Ile Arg Le - #u Ser Lys Met Val Met           370              - #   375              - #   380                           - - Lys Phe Trp Ala Asn Phe Ala Arg Asn Gly As - #n Pro Asn Gly Lys Gly       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Pro His Trp Pro Glu Tyr Asn Gln Lys Gl - #u Gly Tyr Leu Gln         Ile                                                                                              405  - #               410  - #               415              - - Gly Ala Asn Thr Gln Ala Ala Gln Lys Leu Ly - #s Asp Lys Glu Val Ala                   420      - #           425      - #           430                   - - Phe Trp Thr Asn Leu Phe Ala Lys Lys Ala Va - #l Glu Lys Pro Pro Gln               435          - #       440          - #       445                       - - Thr Asp His Ile Glu Leu                                                       450                                                                       __________________________________________________________________________ 

We claim:
 1. A method of enhancing organophosphate detoxifying capability of an esterase chosen from among human acetylcholinesterases, human butrylcholinesterases or human carboxylesterases comprising substituting a histidine residue for at least one amino acid within 6 Å of an active site serine.
 2. A method of claim 1 wherein the histidine substitution is next to the serine.
 3. A method of claim 1 wherein the esterase is human acetylcholinesterase or human butrylcholinesterase.
 4. A method of claim 1 wherein the esterase is human carboxylesterase.
 5. A method of detoxifying an organophosphate comprising the steps of:(1) modifying an esterase chosen from among acetylcholinesterases, butrylcholinesterases or carboxylesterases to enhance organophosphate-detoxifying capability of said esterase by substituting a histidine residue for at least one amino acid within 6 Å of an active site serine of said esterase, and (2) contacting the organophosphate with at least one of the esterases produced in step (1).
 6. A method of claim 5 wherein the esterase is a cholinesterase.
 7. A method of claim 6 wherein the esterase is human butyryl cholinesterase.
 8. A method of claim 6 wherein the esterase is acetylcholinesterase.
 9. A method of claim 5 wherein the esterase is a carboxylesterase.
 10. An esterase of the formula:

    Met His Ser Lys Val Thr Ile Ile Cys Ile Arg Phe Leu Phe Trp                                                        (Seq. #2)                                     - Phe Leu Leu Leu Cys Met Leu Ile Gly Lys Ser His Thr Glu Asp                  - Asp Ile Ile Ile Ala Thr Lys Asn Gly Lys Val Arg Gly Met Asn                  - Leu Thr Val Phe Gly Gly Thr Val Thr Ala Phe Leu Gly Ile Pro                  - Tyr Ala Gln Pro Pro Leu Gly Arg Leu Arg Phe Lys Lys Pro Gln                  - Ser Leu Thr Lys Trp Ser Asp Ile Trp Asn Ala Thr Lys Tyr Ala                  - Asn Ser Cys Cys Gln Asn Ile Asp Gln Ser Phe Pro Gly Phe His                  - Gly Ser Glu Met Trp Asn Pro Asn Thr Asp Leu Ser Glu Asp Cys                  - Leu Tyr Leu Asn Val Trp Ile Pro Ala Pro Lys Pro Lys Asn Ala                  - Thr Val Leu Ile Trp Ile Tyr Gly Gly His Phe Gln Thr Gly Thr                  - Ser Ser Leu His Val Tyr Asp Gly Lys Phe Leu Ala Arg Val Glu                  - Arg Val Ile Val Val Ser Met Asn Tyr Arg Val Gly Ala Leu Gly                  - Phe Leu Ala Leu Pro Gly Asn Pro Glu Ala Pro Gly Asn Met Gly                  - Leu Phe Asp Gln Gln Leu Ala Leu Gln Trp Val Gln Lys Asn Ile                  - Ala Ala Phe Gly Gly Asn Pro Lys Ser Val Thr Leu Phe Gly Glu                  - Ser Ala Gly Ala Ala Ser Val Ser Leu His Leu Leu Ser Pro Gly                  - Ser His Ser Leu Phe Thr Arg Ala Ile Leu Gln Ser Gly Ser Phe                  - Asn Ala Pro Trp Ala Val Thr Ser Leu Tyr Glu Ala Arg Asn Arg                  - Thr Leu Asn Leu Ala Lys Leu Thr Gly Cys Ser Arg Glu Asn Glu                  - Thr Glu Ile Ile Lys Cys Leu Arg Asn Lys Asp Pro Gln Glu Ile                  - Leu Leu Asn Glu Ala Phe Val Val Pro Tyr Gly Thr Pro Leu Ser                  - Val Asn Phe Gly Pro Thr Val Asp Gly Asp Phe Leu Thr Asp Met                  - Pro Asp Ile Leu Leu Glu Leu Gly Gln Phe Lys Lys Thr Gln Ile                  - Leu Val Gly Val Asn Lys Asp Glu Gly Thr Ala Phe Leu Val Tyr                  - Gly Ala Pro Gly Phe Ser Lys Asp Asn Asn Ser Ile Ile Thr Arg                  - Lys Glu Phe Gln Glu Gly Leu Lys Ile Phe Phe Pro Gly Val Ser                  - Glu Phe Gly Lys Glu Ser Ile Leu Phe His Tyr Thr Asp Trp Val                  - Asp Asp Gln Arg Pro Glu Asn Tyr Arg Glu Ala Leu Gly Asp Val                  - Val Gly Asp Tyr Asn Phe Ile Cys Pro Ala Leu Glu Phe Thr Lys                  - Lys Phe Ser Glu Trp Gly Asn Asn Ala Phe Phe Tyr Tyr Phe Glu                  - His Arg Ser Ser Lys Leu Pro Trp Pro Glu Trp Met Gly Val Met                  - His Gly Tyr Glu Ile Glu Phe Val Phe Gly Leu Pro Leu Glu Arg                  - Arg Asp Asn Tyr Thr Lys Ala Glu Glu Ile Leu Ser Arg Ser Ile                  - Val Lys Arg Trp Ala Asn Phe Ala Lys Tyr Gly Asn Pro Asn Glu                  - Thr Gln Asn Asn Ser Thr Ser Trp Pro Val Phe Lys Ser Thr Glu                  - Gln Lys Tyr Leu Thr Leu Asn Thr Glu Ser Thr Arg Ile Met Thr                  - Lys Leu Arg Ala Gln Gln Cys Arg Phe Trp Thr Ser Phe Phe Pro                  - Lys Val Leu Glu Met Thr Gly Asn Ile Asp Glu Ala Glu Trp Glu                  - Trp Lys Ala Gly Phe His Arg Trp Asn Asn Tyr Met Met Asp Trp                  - Lys Asn Gln Phe Asn Asp Tyr Thr Ser Lys Lys Glu Ser Cys Val                  - Gly Leu.                                                              